Differential effects of methamphetamine on Na+/Cl--dependent transporters

It has been demonstrated that methamphetamine (METH) administration affects Na+ /Cl--dependent transporters; for example, METH treatment rapidly and r eversibly decreases dopamine (DA) and serotonin (5HT) transporter function in rat striatum in vivo, as assessed in synaptosomes prepared from METH-tre ated rats. Because acute effects of METH on other transporters within this family have been less studied, the responses of norepinephrine (NE) and gam ma-aminobutyric acid (GABA) transporters to METH administration(s) were det ermined. Both single and multiple METH administrations inhibited hippocampa l NE uptake 1 h after METH treatment(s). In contrast, striatal GABA uptake was not affected by either treatment paradigm. The effects observed after b oth single and multiple METH administrations on NE transporters were attrib utable to increases in K-m with no changes in V-max; effects that were elim inated by repeated washing of the synaptosomes. These 'washout' data sugges t that residual METH introduced by the in vivo subcutaneous injection(s) di rectly reduced NE transporter activity in the in vitro assay and that, unli ke DA and 5HT transporters, METH did not indirectly alter NE transporter fu nction. Taken together, these data demonstrate differences in the responses of NE, GABA, DA, and 5HT transporters to METH treatment. (C) 2000 Elsevier Science B.V. All rights reserved.